SPINAL OPIOID ANALGESIC EFFECTS ARE ENHANCED IN A MODEL OF UNILATERAL INFLAMMATION HYPERALGESIA - POSSIBLE INVOLVEMENT OF NORADRENERGIC MECHANISMS
SPINAL OPIOID ANALGESIC EFFECTS ARE ENHANCED IN A MODEL OF UNILATERAL INFLAMMATION HYPERALGESIA - POSSIBLE INVOLVEMENT OF NORADRENERGIC MECHANISMS
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DOI：
10.1016/0014-2999(91)90097-a
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发表时间：
1991-03-05
影响因子：
5
通讯作者：
DUBNER, R
中科院分区：
文献类型：
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作者：
HYLDEN, JLK;THOMAS, DA;DUBNER, R
我们在一个短期、单侧、卡拉胶诱导的炎症/痛感过敏模型中检测了阿片激动剂和拮抗剂的脊髓镇痛活性。大鼠在测试对有害热刺激的后爪戒断潜伏期前3-24小时接受单次s.c注射卡拉胶（2-6 mg生理盐水）。与对侧未发炎的后爪相比，鞘内给药具有mu-和/或delta-阿片活性的激动剂的剂量-反应曲线向左移动。选择性kappa受体激动剂u -50,488在炎症或非炎症的爪子上给予鞘内时，在这个镇痛实验中没有活性。然而，全身给药u -50,488确实显著提高了发炎爪子的脱爪潜伏期。-2肾上腺素能受体激动剂可乐定在全身或鞘内给药后的足部停药试验中也产生剂量依赖性的抗痛感。与未发炎的爪子相比，发炎的后爪对可乐定的抗伤感受作用明显更敏感。阿片拮抗剂纳洛酮或α -2-肾上腺素受体拮抗剂咪唑嗪可阻断吗啡对炎症后肢的抗痛觉作用。可乐定的作用仅被咪唑嗪阻断。单独使用拮抗剂对戒断潜伏期无显著影响。这些数据表明，阿片类药物在炎症条件下的镇痛作用可能取决于与脊髓去甲肾上腺素能通路的相互作用。
We have examined the spinal analgesic activity of opioid agonists and antagonists in a model of short term, unilateral, carrageenan-induced inflammation/hyperalgesia. Rats received a single s.c. injection of carrageenan (2-6 mg in saline) 3-24 h prior to testing hindpaw withdrawal latencies to noxious thermal stimuli. Dose-response curves for intrathecally administered agonists with mu- and/or delta-opioid activity were shifted to the left for inflamed hindpaws when compared to contralateral non-inflamed paws. The selective kappa-receptor agonist U-50,488H had no activity in this analgesic assay on either inflamed or non-inflamed paws when administered intrathecally. However, systemic administration of U-50,488H did produce significant elevations of paw withdrawal latencies in inflamed paws. The alpha-2-adrenoceptor agonist clonidine also produced dose-dependent antinociception in the paw withdrawal assay after systemic or intrathecal administration. Inflamed hindpaws were significantly more sensitive to the antinociceptive effects of clonidine than were non-inflamed paws. The antinociceptive effect of morphine on inflamed hindpaws was blocked by the opioid antagonist naloxone or the alpha-2-adrenoceptor antagonist idazoxan. The effect of clonidine was only blocked by idazoxan. Antagonists alone had no significant effect on withdrawal latencies. The data indicate that the analgesic action of opioids during conditions of inflammation may depend on an interaction with spinal noradrenergic pathways.